Day three of quarantine for me. My institution is doing the right thing by sending us home. Shutting down laboratory research sucks, but by being cautious and practicing social distancing, we will survive, stay healthy, and be able to get back to work after this necessary pause. I’m privileged to have an employer that recognizes the necessity of these measures, and thanks to National Institutes of Health measures, I’ll still be paid. So my plan is to catch up on scientific literature review, write a review paper, and work with my student remotely on her manuscript in preparation.

I also plan to blog, to write, to spread a bit of information, humor, and hope through the Internet to folks near and far, starting with this post. I’ll cover a bit about the science behind the covid-19 virus – the type of virus, its origin, its mode of spread, and its capacity for mutation and formation of unique strains. Then, I’ll provide information and links to resources to help minimize the risk to cancer patients actively recovering from surgery, on chemotherapy and radiation therapy, and the general considerations patients and survivors should consider during this pandemic.

First, some nomenclature (fancy term for naming things): The virus is actually called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), formerly known as the 2019 novel Coronavirus (2019nCoV). The virus causes the Coronavirus Disease 2019 (COVID-19). Covid-19 is used interchangeably by the media and government agencies for both the virus and the disease it causes. It’s related to the SARS-CoV virus that caused severe acute respiratory syndrome in 2002-2003, as well as MERS-Cov (Middle East Respiratory Syndrome). They are a part of the Betacoronavirus genus, which are characterized by a viral envelop and positive-strand RNA. What does that mean?

Structure: As you can see from the transmission electron micrograph on the left, the virus is round, and its internal contents are surrounded by an envelop. the spiky protrusions sticking out from that envelop are actually proteins. This inspired the name of this type of virus, as these proteins make the virus look like a crown. These proteins include: (1) clusters of the Spike, or S proteins, latch onto a specific protein on the target cell (receptor molecule), and also help the virus fuse to the target cell membrane and become internalized by the target cell; (2) the Membrane (M) glycoproteins are under the spikes, where they help maintain the shape of viral particles and bind to the inner layers of the virus; (3) Lipid (fat) is taken from host cell membranes during previous infections and incorporated into the viral particle; (4) Envelope (E) glycoproteins help assemble new viral particles and help with release and infectious properties of newly-formed viruses; (5) Nucleocapsid (N) proteins that bind and package the RNA genome also help the virus hide from the host immune system. See figures below.

Viral Replication and Infection: These viruses break the rules of the Central Dogma of Molecular Biology (i.e. genetic information flows from DNA to RNA to protein – see previous post). Their genetic information is stored as RNA, which is normally the intermediate cells use to create proteins from the genes encoded by DNA. This works to their advantage, since they trick the infected host cell into translating viral RNA encoding the structural proteins that protect the virus, as well as protein processing. They also trick the host cell into replicating the viral RNA genome and packaging it into new viral particles that are then released from the cell to infect other host cells, as shown in the figure below. The cell surface receptor for SARS-CoV-2 is angiotensin-converting enzyme 2 (ACE2), which is expressed on, among other cell types, lung epithelial cells.

One of the most insidious things viruses do is adapt rapidly through mutation of their RNA genomes. This property is actually what allowed both the original SARS-CoV coronavirus and SARS-CoV-2 to cross species and become infectious to humans (zoonotic). SARS-CoV-2 may have originated in bats, and likely made the jump to humans in a wet animal market in Wuhan, China where domestic and wild animals were slaughtered for meat on site, allowing blood and meat from multiple species to mingle (some of the first patients were epidemiologically linked to the market in Wuhan – Reference Khan et al. J. Clin. Microbiol. doi:10.1128/JCM.00187-20 – hit me up for PDF since the article is not yet publicly available). Many infected individuals can be asymptomatic (not sick) while spreading the virus, which makes it even scarier (Lai et al., 2020, Journal of Microbiology, Immunology, and Infection, in press – hit me up for the PDF since the article is not yet publicly available).

Symptoms: Quoted from Khan et al. J. Clin. Microbiol. doi:10.1128/JCM.00187-10 “Clinical features associated with patients infected with SARS-CoV, MERS-CoV and SARS-CoV-2 range from mild respiratory illness to severe acute respiratory disease (1, 17). Both MERS and SARS patients in later stages develop respiratory distress and renal failure (1, 17). Pneumonia appears to be the most frequent manifestation of SARS-CoV-2 infection, characterized primarily by fever, cough, dyspnea, and bilateral infiltrates on chest imaging (17). The period from infection to appearance of symptoms varies. Generally, it is thought to be 14 days, however, a research group at Guangzhou Medical University reported the incubation period to be 24 days. In a family cluster of infections, the onset of fever and respiratory symptoms occurred approximately three to six days after presumptive exposure (41).” Testing for SARS-CoV-2 is performed by using reverse transcriptase polymerase chain reaction (RT-PCR) to amplify viral RNA in samples from patient until levels are high enough to detect.

Treatments: The bad news is that there are no effective treatments for SARS-CoV-2 infected individuals, though pre-clinical testing for remdesivir and chloroquine shows promise, and existing anti-viral targeting approaches may warrant testing. Vaccines are being developed, but will likely not be validated and available for several months to over a year. The best strategies include social isolation to prevent spread, and management of symptoms for infected individuals (but perhaps avoid ibuprofen to be safe). Reinfection is also possible.

What does this mean for cancer patients and survivors? People with cancer and people who are in active cancer treatment may be at higher risk for SARS-CoV-2 infection and severity of Covid-19 Respiratory Sydrome. Survivors not currently in treatment should not be at higher risk, but check with your healthcare team about the effects of ongoing systemic therapies and increased risk. The American Society of Clinical Oncology (ASCO) is sharing and updating information for cancer patients on their blog, and their recommendations as of March 18, 2020, include:

• Be sure to have enough essential medications, both prescription and over-the-counter, to last for up to a month.
• Create an emergency contact list that includes family, friends, neighbors, and community or neighborhood resources who may be able to provide information or assistance to you if you need it.
• Finally, if you are scheduled for cancer treatments during the COVID-19 outbreak, have a discussion with your oncologist about the benefits and risks of continuing or delaying treatment.

These are additional measures, and cancer patients should definitely follow the social-distancing, frequent hand-washing, avoidance of touching face (eyes, nose, mouth) with hands, and avoidance of close contact with sick people. They do not recommend face masks as a way to prevent COVID-19. But if you’re sick with a respiratory illness, like flu or COVID-19, wearing a face mask could prevent the illness from spreading to those around you.

Bottom line: Stay in touch with your healthcare team for guidance on how to minimize exposure risk during ongoing cancer treatments, and follow general population guidelines for social-distancing, hand washing, and disinfection. Wishing you all continued health and safety!